Feedback produces stem cell and transit amplifying cell behaviors. A two-stage cell lineage is shown, in which cells of type 0 and type 1 divide (at rates v0 and v1, respectively), and produce progeny with an intrinsic probability (p0 or p1, respectively) of remaining at the same lineage stage (as opposed to differentiating to the next one). Cell type 2 is terminally differentiated, and dies (or is shed) at rate d. As long as p0 > 0.5, any negative feedback (schematized by solid red lines, and quantified by parameters g1 and g2) from cell type 2 onto p0 forces the system to reach a self-maintaining steady state. If there is feedback onto both p0 and p1, the quantitative details determine whether cell type 0 behaves like a stem cell and cell type 1 like a transit amplifying cell; or whether cell type 1 behaves like a stem cell and cell type 0 goes extinct. If feedback also slows cell division (for example, v0, dashed red line), more complex system behaviors may occur (for example, in which cell type 1 normally fulfills most stem cell functions, with cell type 0 remaining quiescent except following tissue injury, when it transiently 'reawakens'). For further details see [7,14,17].
Lander Journal of Biology 2009 8:70 doi:10.1186/jbiol177